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    Cyclic depsipeptides and drugs containing the same as the active ingredient
    5.
    发明授权
    Cyclic depsipeptides and drugs containing the same as the active ingredient 失效
    循环利肽和含有与活性成分相同的药物

    公开(公告)号：US06858585B1

    公开(公告)日：2005-02-22

    申请号：US09147434

    申请日：1997-06-25

    申请人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    发明人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    IPC分类号： A61K38/00 ,  C07K7/06 ,  A61K38/15 ,  C07K7/00

    CPC分类号： C07K7/06 ,  A61K38/00

    摘要： Cyclic depsipeptides represented by the formula wherein: R is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15-carbon atoms; A, B, D, E and F independently each other are alanine, valine, leucine, isoleucine, phenylalanine, etc.; W and Z independently each other are aspartic acid, asparagine, glutamic acid or glutamine; and m and n independently each other is 0 or 1, or pharmacologically acceptable salts thereof. The present compounds are prepared according to a method conventionally used in peptide synthesis. The present compounds are useful as an agent for promoting the production of apolipoprotein E, a therapeutic agent for neurologic damages, a therapeutic agent for dementia, an agent for inhibiting the production of apolipoprotein B, an agent for promoting the production of apolipoprotein A1 or a therapeutic agent for hyperlipemia.

    摘要翻译： 以下式表示的环状缩酚酸酯：R为5-20个碳原子的直链或支链烷基或5-15个碳原子的直链或支链烷氧基甲基; A，B，D，E和F独立地为丙氨酸，缬氨酸，亮氨酸，异亮氨酸，苯丙氨酸等; W和Z独立地是天冬氨酸，天冬酰胺，谷氨酸或谷氨酰胺; m和n彼此独立地为0或1，或其药理学上可接受的盐。 本发明化合物根据肽合成中常规使用的方法制备。 本发明化合物可用作促进载脂蛋白E的产生，神经损伤治疗剂，痴呆治疗剂，抑制载脂蛋白B的制备的试剂，促进载脂蛋白A1的制造的试剂或 高脂血症治疗剂。

    Bicyclic depsipeptides
    6.
    发明授权
    Bicyclic depsipeptides 失效
    双环脱肽

    公开(公告)号：US06211145B1

    公开(公告)日：2001-04-03

    申请号：US09212481

    申请日：1998-12-16

    申请人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    发明人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    IPC分类号： A61K3808

    CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K7/56 ,  C07K7/64

    摘要： The present invention provides a bicyclic depsipeptide having the formula (1) wherein: R is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; A, D, E and J independently are a residue of an amino acid selected from the group of alanine, valine, leucine, etc.; B and F are the same or different and a residue of an amino acid selected from the group consisting of cysteine, aspartic acid, glutamic acid, lysine, hydroxylysine and serine; G is a disulfide bond, an amido bond or an ester bond; W is a residue of an amino acid selected from the group consisting of aspartic acid and glutamic acid; Z is a residue of an amino acid selected from the group consisting of aspartic acid, asparagine, glutamic acid and glutamine; l, m, n, p and q independently are 0 or 1; or a pharmacologically acceptable salt thereof.

    摘要翻译： 本发明提供具有式（1）的双环脱肽酶，其中：R是5-20个碳原子的直链或支链烷基或5-15个碳原子的直链或支链烷氧基甲基; A，D，E和J独立地是选自丙氨酸，缬氨酸，亮氨酸等的氨基酸的残基; B和F相同或不同，并且选自半胱氨酸，天冬氨酸，谷氨酸，赖氨酸，羟赖氨酸和丝氨酸的氨基酸残基; G是二硫键，酰胺键或酯键; W是选自天冬氨酸和谷氨酸的氨基酸残基; Z是选自天冬氨酸，天冬酰胺，谷氨酸和谷氨酰胺的氨基酸的残基; l，m，n，p和q独立地为0或1; 或其药理学上可接受的盐。

    Depsipeptides and drugs containing the same as the active ingredient
    7.
    发明授权
    Depsipeptides and drugs containing the same as the active ingredient 有权
    含有与活性成分相同的多肽和药物

    公开(公告)号：US06255286B1

    公开(公告)日：2001-07-03

    申请号：US09214002

    申请日：1998-12-24

    申请人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    发明人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    IPC分类号： A61K3800

    CPC分类号： C07K5/1021 ,  A61K38/00 ,  C07K5/06043 ,  C07K5/06052 ,  C07K5/06104 ,  C07K5/101 ,  C07K7/06 ,  C07K11/00

    摘要： Depsipeptides represented by the formula (1): (wherein: R1 is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; R2 is —A—B, —A—B—W, —A—B—W—D or —A—B—W—D—E, R3 is a hydroxyl group, a lower alkoxy group, a benzyloxy group, —Z, —Z—G or —Z—G—J, the above A, B, D, E, G and J independently each other are a residue of an amino acid selected from alanine, valine, leucine, isoleucine, serine, threonine, lysine, hydroxylysine, arginine, cysteine, methionine, phenylalanine, tyrosine, aspartic acid, asparagine, glutamic acid, glutamine and the like or an N—(C1-C4) alkyl derivative of these amino acid residues; the above W and Z independently each other are a residue of an amino acid selected from aspartic acid, asparagine, glutamic acid, glutamine, alanine, serine or lysine) or pharmacologically acceptable salts thereof. The depsipeptides have an activity of promoting the production of apolipoprotein E and are useful as a therapeutic agent for neurologic damages, especially for dementia, and further as a therapeutic agent for hyperlipemia.

    摘要翻译： 由式（1）表示的缩肽：其中：R1是5-20个碳原子的直链或支链烷基或5-15个碳原子的直链或支链烷氧基甲基; R2是-AB，-ABW，-ABWD 或-ABWDE，R3是羟基，低级烷氧基，苄氧基，-Z，-ZG或-ZGJ，上述A，B，D，E，G和J彼此独立地是氨基的残基 选自丙氨酸，缬氨酸，亮氨酸，异亮氨酸，丝氨酸，苏氨酸，赖氨酸，羟赖氨酸，精氨酸，半胱氨酸，甲硫氨酸，苯丙氨酸，酪氨酸，天冬氨酸，天冬酰胺，谷氨酸，谷氨酰胺等的N-酸或N-（C1-C4） 这些氨基酸残基的烷基衍生物;上述W和Z彼此独立地是选自天冬氨酸，天冬酰胺，谷氨酸，谷氨酰胺，丙氨酸，丝氨酸或赖氨酸的氨基酸的残基）或其药理学上可接受的盐。脱脂肽具有 促进载脂蛋白E的产生的活性并且可用作治疗 用于神经损伤的特异剂，特别是对于痴呆，并且作为高脂血症的治疗剂。

    Depsipeptides containing N-substituted glycine residue
    8.
    发明授权
    Depsipeptides containing N-substituted glycine residue 失效
    含有N-取代的甘氨酸残基的三肽

    公开(公告)号：US06316406B1

    公开(公告)日：2001-11-13

    申请号：US09379614

    申请日：1999-08-24

    申请人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    发明人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    IPC分类号： A61K3815

    CPC分类号： C07K7/06 ,  A61K38/00

    摘要： A depsipeptide containing N-substituted glycine residue having the formula (1) or (2): (wherein R1 is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; R2 is a group of the formula —A—B—W—(D)m—(E)n, —A—B—W—(D)m—(E)n—F or —A—B—W—(D)m—(E)n—F—Z; R3 is a hydroxyl group, a lower alkoxy group, a benzyloxy group, or a group of the formula —Z, —Z—G or —Z—G—J; A, B, D, E, F, G and J independently are an N-substituted glycine residue or a residue of an amino acid selected from the group consisting of alanine, valine, leucine, serine, etc.; W and Z independently are a residue of an amino acid selected from the group consisting of an aspartic acid, a glutamic acid, etc.; at least one of A, B, D, E, F, G and J is an N-substituted glycine residue) or a pharmacologically acceptable salt thereof. The above depsipeptides have a promoting activity on the production of apolipoprotein E, and are useful as a therapeutic agent for neurologic damages, especially dementia, and hyperlipemia.

    摘要翻译： 含有具有式（1）或（2）的N-取代甘氨酸残基的缩酚酸肽:(其中R 1是5-20个碳原子的直链或支链烷基或5-15个碳原子的直链或支链烷氧基甲基; R2 是式-ABW-（D）m-（E）n，-ABW-（D）m-（E）nF或-ABW-（D）m-（E）nFZ的基团; R3是羟基 ，低级烷氧基，苄氧基或式-Z，-ZG或-ZGJ的基团; A，B，D，E，F，G和J独立地为N-取代的甘氨酸残基或 选自丙氨酸，缬氨酸，亮氨酸，丝氨酸等的氨基酸; W和Z独立地是选自天冬氨酸，谷氨酸等的氨基酸的残基;至少 A，B，D，E，F，G和J之一是N-取代的甘氨酸残基）或其药理学上可接受的盐。 上述脱脂肽对载脂蛋白E的产生具有促进作用，可用作神经损伤的治疗剂，特别是痴呆和高脂血症。

    Depsipeptides containing N-substituted glycine residue
    9.
    发明授权
    Depsipeptides containing N-substituted glycine residue 失效
    含有N-取代的甘氨酸残基的三肽

    公开(公告)号：US6001815A

    公开(公告)日：1999-12-14

    申请号：US218125

    申请日：1998-12-21

    申请人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    发明人： Makoto Yanai ,  Masashi Suzuki ,  Norio Oshida ,  Koji Kawamura ,  Shigeru Hiramoto ,  Orie Yasuda ,  Nobuhiro Kinoshita ,  Akiko Shingai ,  Masako Takasu

    IPC分类号： A61K38/00 ,  C07K7/06

    CPC分类号： C07K7/06 ,  A61K38/00

    摘要： A depsipeptide containing N-substituted glycine residue having the formula (1) or (2): ##STR1## (wherein R.sub.1 is a straight or branched alkyl group of 5-20 carbon atoms or a straight or branched alkoxymethyl group of 5-15 carbon atoms; R.sub.2 is a group of the formula --A--B--W--(D).sub.m --(E).sub.n, --A--B--W--(D).sub.m --(E).sub.n --F or --A--B--W--(D).sub.m --(E).sub.n --F--Z; R.sub.3 is a hydroxyl group, a lower alkoxy group, a benzyloxy group, or a group of the formula --Z, --Z--G or --Z--G--J; A, B, D, E, F, G and J independently are an N-substituted glycine residue or a residue of an amino acid selected from the group consisting of alanine, valine, leucine, serine, etc.; W and Z independently are a residue of an amino acid selected from the group consisting of an aspartic acid, a glutamic acid, etc.; at least one of A, B, D, E, F, G and J is an N-substituted glycine residue) or a pharmacologically acceptable salt thereof.The above depsipeptides have a promoting activity on the production of apolipoprotein E, and are useful as a therapeutic agent for neurologic damages, especially dementia, and hyperlipemia.

    摘要翻译： 含有具有式（1）或（2）的N-取代甘氨酸残基的depsipeptide：（其中R1是5-20个碳原子的直链或支链烷基或5-15个碳原子的直链或支链烷氧基甲基; R2 是式-ABW-（D）m-（E）n，-ABW-（D）m-（E）nF或-ABW-（D）m-（E）nFZ的基团; R3是羟基 ，低级烷氧基，苄氧基或式-Z，-ZG或-ZGJ的基团; A，B，D，E，F，G和J独立地为N-取代的甘氨酸残基或 选自丙氨酸，缬氨酸，亮氨酸，丝氨酸等的氨基酸; W和Z独立地是选自天冬氨酸，谷氨酸等的氨基酸的残基;至少 A，B，D，E，F，G和J之一是N-取代的甘氨酸残基）或其药理学上可接受的盐。 上述脱脂肽对载脂蛋白E的产生具有促进作用，可用作神经损伤的治疗剂，特别是痴呆和高脂血症。